Shibasaki F, Price E R, Milan D, McKeon F
Department of Cell Biology, Harvard Medical School, Boston, Massacusetts 02115, USA.
Nature. 1996 Jul 25;382(6589):370-3. doi: 10.1038/382370a0.
A new facet of calcium signalling involves the nuclear import of the NF-AT transcription factors from their dormant position in the cytoplasm. The protein phosphatase calcineurin appears to play an essential role in activating NF-AT nuclear import, as the calcineurin inhibitors cyclosporin A and FK506 block dephosphorylation and nuclear import of NF-AT (refs 4-7). Here we show that calcium signalling induces an association between NF-AT4 and calcineurin, and that these molecules are transported, as a complex, to the nucleus, where calcineurin continues to dephosphorylate NF-AT4. We propose that a nuclear complex of NF-AT4 and calcineurin maintains calcium signalling by counteracting a vigorous nuclear NF-AT kinase.
钙信号传导的一个新方面涉及核因子活化T细胞（NF-AT）转录因子从其在细胞质中的休眠位置向细胞核的转运。蛋白磷酸酶钙调神经磷酸酶似乎在激活NF-AT的核转运中起关键作用，因为钙调神经磷酸酶抑制剂环孢菌素A和FK506可阻断NF-AT的去磷酸化及核转运（参考文献4 - 7）。在此我们表明，钙信号传导诱导了NF-AT4与钙调神经磷酸酶之间的结合，并且这些分子作为一个复合物被转运至细胞核，在细胞核中钙调神经磷酸酶继续使NF-AT4去磷酸化。我们提出，NF-AT4与钙调神经磷酸酶的核复合物通过对抗一种活跃的核NF-AT激酶来维持钙信号传导。
